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1.
Phys Med Biol ; 69(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38821109

RESUMO

Objective.The validation of deformable image registration (DIR) for contour propagation is often done using contour-based metrics. Meanwhile, dose accumulation requires evaluation of voxel mapping accuracy, which might not be accurately represented by contour-based metrics. By fabricating a deformable anthropomorphic pelvis phantom, we aim to (1) quantify the voxel mapping accuracy for various deformation scenarios, in high- and low-contrast regions, and (2) identify any correlation between dice similarity coefficient (DSC), a commonly used contour-based metric, and the voxel mapping accuracy for each organ.Approach. Four organs, i.e. pelvic bone, prostate, bladder and rectum (PBR), were 3D printed using PLA and a Polyjet digital material, and assembled. The latter three were implanted with glass bead and CT markers within or on their surfaces. Four deformation scenarios were simulated by varying the bladder and rectum volumes. For each scenario, nine DIRs with different parameters were performed on RayStation v10B. The voxel mapping accuracy was quantified by finding the discrepancy between true and mapped marker positions, termed the target registration error (TRE). Pearson correlation test was done between the DSC and mean TRE for each organ.Main results. For the first time, we fabricated a deformable phantom purely from 3D printing, which successfully reproduced realistic anatomical deformations. Overall, the voxel mapping accuracy dropped with increasing deformation magnitude, but improved when more organs were used to guide the DIR or limit the registration region. DSC was found to be a good indicator of voxel mapping accuracy for prostate and rectum, but a comparatively poorer one for bladder. DSC > 0.85/0.90 was established as the threshold of mean TRE ⩽ 0.3 cm for rectum/prostate. For bladder, extra metrics in addition to DSC should be considered.Significance. This work presented a 3D printed phantom, which enabled quantification of voxel mapping accuracy and evaluation of correlation between DSC and voxel mapping accuracy.


Assuntos
Pelve , Imagens de Fantasmas , Humanos , Pelve/diagnóstico por imagem , Doses de Radiação , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Masculino , Impressão Tridimensional
2.
Phys Med ; 122: 103380, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38805761

RESUMO

INTRODUCTION: Real-time gated proton therapy (RGPT) is a motion management technique unique to the Hitachi particle therapy system. It uses pulsed fluoroscopy to track an implanted fiducial marker. There are currently no published guidelines on how to conduct the commissioning and quality assurance. In this work we reported on our centre's commissioning workflow and our daily and monthly QA procedures. METHODS: Six commissioning measurements were designed for RGPT. The measurements include imaging qualities, fluoroscopic exposures, RGPT marker tracking accuracy, temporal gating latency, fiducial marker tracking fidelity and an end-to-end proton dosimetry measurement. Daily QA consists of one measurement on marker localization accuracy. Four months daily QA trends are presented. Monthly QA consists of three measurementson the gating latency, fluoroscopy imaging quality and dosimetry verification of gating operation with RGPT. RESULTS: The RGPT was successfully commissioned in our centre. The air kerma rates were within 15 % from specifications and the marker tracking accuracies were within 0.245 mm. The gating latencies for turning the proton beam on and off were 119.5 and 50.0 ms respectively. The 0.4x10.0 mm2 Gold AnchorTM gave the best tracking results with visibility up to 30 g/cm2. Gamma analysis showed that dose distribution of a moving and static detectors had a passing rate of more than 95 % at 3 %/3mm. The daily marker localization QA results were all less than 0.2 mm. CONCLUSION: This work could serve as a good reference for other upcoming Hitachi particle therapy centres who are interested to use RGPT as their motion management solution.


Assuntos
Terapia com Prótons , Garantia da Qualidade dos Cuidados de Saúde , Terapia com Prótons/instrumentação , Marcadores Fiduciais , Radiometria , Fatores de Tempo , Fluoroscopia , Controle de Qualidade , Humanos , Radioterapia Guiada por Imagem
3.
Phytochemistry ; 223: 114113, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38697241

RESUMO

Eleven undescribed cembrane-type diterpenoids, named litoamentenes A-K (1-11), were isolated from the soft coral Litophyton amentaceum collected from the South China Sea. Their structures were elucidated by extensive analysis of spectroscopic data, comparison with the literature data, single crystal X-ray diffraction, quantum chemical calculations and TDDFT-ECD calculations. This is the first systematic investigation of L. amentaceum. In particular, compounds 1-3 are cembrane-type norditerpenoids that lack isopropyl side chains. Compound 6 is a cembrane-type norditerpenoid without a methyl group at C-4, the first natural product identified with this carbon skeleton. Compounds 6, 9 and 10 showed modest cytotoxicity against several human cancer cell lines with IC50 values ranging from 3.99 to 14.56 µM.


Assuntos
Antozoários , Diterpenos , Ensaios de Seleção de Medicamentos Antitumorais , Antozoários/química , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , Animais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , China , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Modelos Moleculares
4.
J Appl Clin Med Phys ; 25(7): e14348, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38561975

RESUMO

INTRODUCTION: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3. METHODS: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread-out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented. RESULTS: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ± 3 % $ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ± 1 mm $ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ± 10 cm $ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5 mm $1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries. CONCLUSION: With the proposed approach, we can perform four QA items in the TG224 within 10 min.


Assuntos
Terapia com Prótons , Garantia da Qualidade dos Cuidados de Saúde , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Terapia com Prótons/métodos , Terapia com Prótons/normas , Humanos , Garantia da Qualidade dos Cuidados de Saúde/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Neoplasias/radioterapia , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/normas , Imagens de Fantasmas , Algoritmos , Radiometria/métodos
5.
Phys Med ; 120: 103341, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38554639

RESUMO

BACKGROUND AND PURPOSE: This work introduces the first assessment of CT calibration following the ESTRO's consensus guidelines and validating the HLUT through the irradiation of biological material. METHODS: Two electron density phantoms were scanned with two CT scanners using two CT scan energies. The stopping power ratio (SPR) and mass density (MD) HLUTs for different CT scan energies were derived using Schneider's and ESTRO's methods. The comparison metric in this work is based on the Water-Equivalent Thickness (WET) difference between the treatment planning system and biological irradiation measurement. The SPR HLUTs were compared between the two calibration methods. To assess the accuracy of using MD HLUT for dose calculation in the treatment planning system, MD vs SPR HLUT was compared. Lastly, the feasibility of using a single SPR HLUT to replace two different energy CT scans was explored. RESULTS: The results show a WET difference of less than 3.5% except for the result in the Bone region between Schneider's and ESTRO's methods. Comparing MD and SPR HLUT, the results from MD HLUT show less than a 3.5% difference except for the Bone region. However, the SPR HLUT shows a lower mean absolute percentage difference as compared to MD HLUT between the measured and calculated WET difference. Lastly, it is possible to use a single SPR HLUT for two different CT scan energies since both WET differences are within 3.5%. CONCLUSION: This is the first report on calibrating an HLUT following the ESTRO's guidelines. While our result shows incremental improvement in range uncertainty using the ESTRO's guideline, the prescriptional approach of the guideline does promote harmonization of CT calibration protocols between different centres.


Assuntos
Terapia com Prótons , Prótons , Terapia com Prótons/métodos , Imagens de Fantasmas , Tomografia Computadorizada por Raios X/métodos , Tomógrafos Computadorizados , Calibragem , Água
6.
Phys Imaging Radiat Oncol ; 29: 100552, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38405428

RESUMO

Background and purpose: High-density dental fillings pose a non-negligible impact on head and neck cancer treatment. For proton therapy, stopping power ratio (SPR) prediction will be significantly impaired by the associated image artifacts. Dose perturbation is also inevitable, compromising the treatment plan quality. While plenty of work has been done on metal or amalgam fillings, none has touched on composite resin (CR) and glass ionomer cement (GIC) which have seen an increasing usage. Hence, this work aims to provide a detailed characterisation of SPR and dose perturbation in proton therapy caused by CR and GIC. Materials and methods: Four types of fillings were used: CR, Fuji Bulk (FB), Fuji II (FII) and Fuji IX (FIX). The latter three belong to GIC category. Measured SPR were compared with SPR predicted using single-energy computed tomography (SECT) and dual-energy computed tomography (DECT). Dose perturbation of proton beams with lower- and higher-energy levels was also quantified using Gafchromic films. Results: The measured SPR for CR, FB, FII and FIX were 1.68, 1.77, 1.77 and 1.76, respectively. Overall, DECT could predict SPR better than SECT. The lowest percentage error achieved by DECT was 19.7 %, demonstrating the challenge in estimating SPR, even for fillings with relatively lower densities. For both proton beam energies and all four fillings of about 4.5 mm thickness, the maximum dose perturbation was 3 %. Conclusion: This study showed that dose perturbation by CR and GIC was comparatively small. We have measured and recommended the SPR values for overriding the fillings in TPS.

7.
J Appl Clin Med Phys ; 25(2): e14154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37683120

RESUMO

BACKGROUND: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks. METHODS: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data. RESULTS: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion. CONCLUSION: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement.


Assuntos
Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Algoritmos , Pelve , Radiometria/métodos , Radioterapia de Intensidade Modulada/métodos , Garantia da Qualidade dos Cuidados de Saúde
9.
Phys Med Biol ; 68(22)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37857314

RESUMO

Introduction. Dispersion in an accelerator quantifies the deviation of the proton trajectory when there is a momentum deviation. We present for the first time a safe method of measuring dispersion in the clinic, using a scintillator detector and the momentum deviations within a spill. This is an important accelerator quantity as we found that this is the reason behind the large dose fluctuation in our absolute dosimetry measurement.Methods. Dispersions are measured for nine energies in a Hitachi ProBeat system at three locations (isocenter and at two profile monitors) and at two gantry angles (0 and 90 degrees) by first measuring the spot position and momentum drift within a spill. The spot position drift is measured by the XRV-4000 at the isocenter, and by the two profile monitors located at 0.57 and 2.27 m from the isocenter. The momentum drift is calculated from the intra-spill range drift which is measured using the Ranger accessory. The dispersion at isocenter and its gradient are calculated using the weighted least square regression on the measured dispersions at the three locations. A constraint is formulated on the dispersion and its gradient to ensure minimal intra-spill spot position deviation around the isocenter.Results. The measured intra-spill range and spot positional drift at isocenter are less than0.25mmand0.7mmrespectively. The momentum spread calculated from the range drift are less than 0.08%. The dispersion at the isocenter ranged from0.50to4.30mand the zero-crossing happens upstream of isocenter for all energies. 2 of the 9 energies (168.0 and 187.5 MeV) violated the constraint and has an intra-spill spot positional deviation greater than1.0within5cmfrom the isocenter.Conclusion. This measurement is recommended as part of commissioning and annual quality assurance for accelerator monitoring and to ensure intra-spill spot deviations remain low.


Assuntos
Terapia com Prótons , Terapia com Prótons/métodos , Radiometria , Prótons , Movimento (Física)
10.
Phys Med Biol ; 68(15)2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37437590

RESUMO

Objective. Automatic deformable image registration (DIR) is a critical step in adaptive radiotherapy. Manually delineated organs-at-risk (OARs) contours on planning CT (pCT) scans are deformably registered onto daily cone-beam CT (CBCT) scans for delivered dose accumulation. However, evaluation of registered contours requires human assessment, which is time-consuming and subjects to high inter-observer variability. This work proposes a deep learning model that allows accurate prediction of Dice similarity coefficients (DSC) of registered contours in prostate radiotherapy.Approach. Our dataset comprises 20 prostate cancer patients with 37-39 daily CBCT scans each. The pCT scans and planning contours were deformably registered to each corresponding CBCT scan to generate virtual CT (vCT) scans and registered contours. The DSC score, which is a common contour-based validation metric for registration quality, between the registered and manual contours were computed. A Siamese neural network was trained on the vCT-CBCT image pairs to predict DSC. To assess the performance of the model, the root mean squared error (RMSE) between the actual and predicted DSC were computed.Main results. The model showed promising results for predicting DSC, giving RMSE of 0.070, 0.079 and 0.118 for rectum, prostate, and bladder respectively on the holdout test set. Clinically, a low RMSE implies that the predicted DSC can be reliably used to determine if further DIR assessment from physicians is required. Considering the event where a registered contour is classified as poor if its DSC is below 0.6 and good otherwise, the model achieves an accuracy of 92% for the rectum. A sensitivity of 0.97 suggests that the model can correctly identify 97% of poorly registered contours, allowing manual assessment of DIR to be triggered.Significance. We propose a neural network capable of accurately predicting DSC of deformably registered OAR contours, which can be used to evaluate eligibility for plan adaptation.


Assuntos
Neoplasias de Cabeça e Pescoço , Masculino , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
11.
Polymers (Basel) ; 15(11)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37299299

RESUMO

Non-isocyanate Polyurethane (NIPU) has been known to result from a thermal-ring-opening reaction between bis-cyclic carbonate (BCC) compounds and polyamines. BCC can be obtained from carbon dioxide capture using an epoxidized compound. Microwave radiation has been found to be an alternative process to conventional heating for synthesizing NIPU on a laboratory scale. The microwave radiation process is far more efficient (>1000 times faster) than using a conventional heating reactor. Now, a flow tube reactor has been designed for a continuous and recirculating microwave radiation system for scaling up NIPU. Furthermore, the TOE (Turn Over Energy) of the microwave for a lab batch (24.61 g) reactor was 24.38 kJ/g. This decreased to 8.89 kJ/g with an increase in reaction size of up to 300 times with this new continuous microwave radiation system. This proves that synthesizing NIPU with this newly-designed continuous and recirculating microwave radiation process is not only a reliable energy-saving method, but is also convenient for scale-up, making it a green process.

13.
Braz. j. otorhinolaryngol. (Impr.) ; 88(5): 733-739, Sept.-Oct. 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403920

RESUMO

Abstract Introduction The Epley maneuver is useful for the otoconia to return from the long arm of the posterior semicircular canal into the utricle. To move otoconia out of the posterior semicircular canal short arm and into the utricle, we need different maneuvers. Objective To diagnose the short-arm type BPPV of the posterior semicircular canal and treat them with bow-and-yaw maneuver. Methods 171 cases were diagnosed as BPPV of the posterior semicircular canal based on a positive Dix-Hallpike maneuver. We first attempted to treat patients with the bow-and-yaw maneuver and then performed the Dix-Hallpike maneuver again. If the repeated Dix-Hallpike maneuver gave negative results, we diagnosed the patient with the short-arm type of BPPV of the posterior semicircular canal and considered the patient to have been cured by the bow-and-yaw maneuver; otherwise, probably the long-arm type BPPV of the posterior semicircular canal existed and we treated the patient with the Epley maneuver. Results Approximately 40% of the cases were cured by the bow-and-yaw maneuver, giving negative results on repeated Dix-Hallpike maneuvers, and were diagnosed with short-arm lithiasis. Conclusion The short-arm type posterior semicircular canal BPPV can be diagnosed and treated in a convenient and comfortable manner.


Resumo Introdução A manobra de Epley é útil para o retorno da otocônia do braço longo do canal semicircular posterior para o utrículo. Diferentes manobras são necessárias para mover a otocônia para fora do braço curto do canal semicircular posterior e para dentro do utrículo. Objetivo Diagnosticar a VPPB do tipo braço curto do canal semicircular posterior e tratá-la com a manobra de incline and balance. Método Foram diagnosticados 171 casos como VPPB de canal semicircular posterior com base na manobra de Dix-Hallpike positiva. Primeiro tentamos tratar os pacientes com a manobra de incline and balance e, em seguida, executamos a manobra de Dix-Hallpike novamente. Se a repetição da manobra de Dix-Hallpike desse resultados negativos, diagnosticávamos o paciente como VPPB do canal semicircular posterior do tipo braço curto e considerávamos que ele ou ela havia sido curado pela manobra de incline and balance; caso contrário, provavelmente o paciente apresentava VPPB do canal semicircular posterior do tipo braço longo e tratávamos o paciente com a manobra de Epley. Resultados Aproximadamente 40% dos casos foram curados pela manobra de incline and balance, com resultados negativos nas manobras de Dix-Hallpike repetidas, e foram diagnosticados com litíase de braço curto. Conclusão A VPPB de canal semicircular posterior do tipo braço curto pode ser diagnosticada e tratada de maneira conveniente e confortável.

14.
Diabetes Obes Metab ; 24(11): 2182-2191, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35762489

RESUMO

AIMS: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. MATERIALS AND METHODS: LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. RESULTS: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2 , corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: -0.7 (95% confidence interval: -0.9, -0.6)%; p < .0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p < .0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: -0.9 (95% confidence interval: -1.4, -0.5) kg; p = .0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar. CONCLUSIONS: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Glicemia , China/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Combinação de Medicamentos , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Peptídeos/uso terapêutico
15.
Orthop Surg ; 14(6): 1203-1216, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35470579

RESUMO

OBJECTIVE: To investigate the changes in proinflammatory cytokines and chemokines, namely, C-C motif ligand (CCL) 2 and CCL7, in postmenopausal osteoporosis (PMOP) and to develop a new drug, bindarit (Bnd), for PMOP in an ovariectomized (OVX) mouse model. METHODS: Bone marrow macrophages (BMMs) from the femurs of five women with PMOP and five premenopausal women without osteoporosis were detected by RNA sequencing. BMMs from mice were differentiated into osteoclasts and treated with a synthetic inhibitor of CCL2 and CCL7, Bnd, or 17 beta estradiol (E2 ). Mouse BMMs were differentiated into osteoclasts with or without Bnd for 7 days and analyzed by RNA sequencing. Osteoblasts of mice were induced to undergo osteoblastogenesis and treated with Bnd. OVX mice were treated with E2 or Bnd after surgery. The protein and mRNA expression of CCL2 and CCL7 was detected using immunostaining and qPCR, respectively, in OVX and aged mice and in cells cultured in vitro. Osteoclast formation was detected using a tartrate-resistant acid phosphatase (TRAP) assay in vitro and in vivo. Alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) were detected using immunostaining to evaluate osteogenesis. Microcomputed tomography was conducted to analyze trabecular bone parameters, the structure model index, bone mineral density and other variables. Nuclear factor-κB (NF-κB) signaling pathway-related protein phosphorylation of IKKα/ß (p-IKKα/ß) and p-NFκB p65 was examined using western blotting. RESULTS: CCL2, CCL7 and their receptor of C-C chemokine receptor-2 (CCR2), and the NF-κB signaling pathway, were significantly increased in women with PMOP. CCL2 and CCL7 protein and mRNA expression was increased in OVX mice and aged female mice, but the increases were attenuated by E2 and Bnd. E2 and Bnd effectively inhibited osteoclastogenesis and the protein expression of CCL2 and CCL7 both in vitro and in vivo and reduced bone loss in OVX mice. Bnd did not affect the mineralization of osteoblasts directly in vitro but reduced bone turnover in vivo. p-IKKα/ß and p-NFκB p65 levels were increased in BMMs of mice after differentiation into osteoclasts but were significantly decreased by Bnd. CONCLUSION: The proinflammatory cytokines and chemokines CCL2, CCL7 and CCR2 were correlated with PMOP. Bnd attenuated the increases in CCL2 and CCL7 levels to affect osteoporosis in OVX mice via the NFκB signaling pathway. Thus, Bnd may be useful as a new therapeutic for the prevention of PMOP.


Assuntos
Doenças Ósseas Metabólicas , Reabsorção Óssea , Osteoporose Pós-Menopausa , Osteoporose , Animais , Diferenciação Celular , Quimiocina CCL2 , Quimiocina CCL7 , Citocinas/metabolismo , Feminino , Humanos , Quinase I-kappa B/metabolismo , Quinase I-kappa B/farmacologia , Indazóis , Camundongos , NF-kappa B/metabolismo , Osteoclastos , Osteogênese , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Ovariectomia , Propionatos , RNA Mensageiro/metabolismo , Transdução de Sinais , Microtomografia por Raio-X
16.
J Tradit Chin Med ; 42(2): 221-226, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35473342

RESUMO

OBJECTIVE: To examine the efficacy of Qinghuayin (, QHY) in rat chronic atrophic gastritis (CAG) models and explored the molecular mechanism of QHY in treating CAG. METHODS: In total, 65 Wistar rats were randomly divided into the control (= 10) and CAG groups ( = 55). CAG model rats were further divided into five groups: model ( = 10), vitacoenzyme ( = 10), low-dose QHY ( = 10), medium-dose QHY ( = 10), and high-dose QHY groups ( = 10). We analyzed histopathological changes using hematoxylin and eosin staining and measured interleukin (IL)-6 and IL-8 levels in serum using enzyme-linked immunosorbent assay (ELISA) (Boster Bio, Pleasanton, USA). In addition, gastrin (GAS), pepsinogen I (PGI), and PGII expressions were evaluated using ELISA. The protein and mRNA expression of toll-like receptor 4 (TLR4) and toll or interleukin-1 receptor domain-containing adaptor inducing interferon-ß (TRIF) was detected by Western blotting and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: Our results revealed that histopathological changes in CAG model rates could be restored by low-, medium-, and high-dose QHY. The changes in GAS and PGI/II expression demonstrated that QHY improved CAG. Serum IL-6 and IL-levels were decreased by QHY administration. TLR4 and TRIF were upregulated at the mRNA and protein levels in the model group but downregulated by QHY administration. CONCLUSION: We concluded that QHY could effectively improve the histopathological changes of the gastric mucosa induced by CAG in rats. The therapeutic mechanism of QHY may be related to inhibition of the inflammatory factors IL-6 and IL-8 and suppression of TLR4/TRIF mRNA and protein expression.


Assuntos
Gastrite Atrófica , Interferons , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/farmacologia , Animais , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/genética , Humanos , Interferon beta/metabolismo , Interferon beta/farmacologia , Interferons/farmacologia , Interleucina-6/genética , Interleucina-8/genética , RNA Mensageiro , Ratos , Ratos Wistar , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
17.
Diabetes Obes Metab ; 24(8): 1522-1533, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35441412

RESUMO

AIMS: To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD). MATERIALS AND METHODS: LixiLan-O-AP (NCT03798054) was a 24-week multicentre study in adults (n = 878, mean age 56.0 years, mean body mass index 26.0 kg/m2 ) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%) and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open-label once-daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium-glucose cotransporter-2 inhibitors. The primary efficacy endpoint was change in HbA1c. RESULTS: After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (-21 mmol/mol; -1.9%) compared with iGlar (-16 mmol/mol; -1.4%; P < 0.0001) and Lixi (-10 mmol/mol; -0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2-hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference -1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant-year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%). CONCLUSIONS: iGlarLixi achieved significant HbA1c reductions, to near-normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well-tolerated treatment option for Asian Pacific people with T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Administração Oral , Adulto , Glicemia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Hemoglobinas Glicadas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Metformina/efeitos adversos , Pessoa de Meia-Idade , Peptídeos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Aumento de Peso
18.
Food Chem ; 382: 132571, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35245758

RESUMO

Kimchi is a globally consumed food with diverse health-benefits, but the low-abundance bioactive compounds in kimchi remain largely neglected. Here we show that kimchi contains a family of low-abundance (0.5-1.6 µg/g, dried weight) high-order indole oligomers derived from indole-3-carbinol (I3C), a breakdown product released from cruciferous vegetables used for producing the traditional subsidiary food. The structure determination of such complex molecules was accomplished by synthesizing linear indole oligomers as standard materials followed by the LC-HR-MS analysis. One indole tetramer (LTe2) is substantially toxic to tumor MV4-11 (IC50 = 1.94 µM) and THP-1 cells (IC50 = 7.12 µM). Collectively, the work adds valuable information to the knowledge package about kimchi, and may inspire the generation of indole-based molecules, to which many drugs belong.


Assuntos
Brassicaceae , Alimentos Fermentados , Neoplasias , Brassicaceae/química , Humanos , Indóis/química
19.
ACS Appl Mater Interfaces ; 13(8): 9846-9855, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33594888

RESUMO

Two types of ion-conducting polyimides with sulfonate or ether functional groups were synthesized as ion-type or coordination-type cathode binders for lithium-ion batteries (LIBs), respectively. Although superior ion transport abilities have been reported for both types of ion-conducting polymers, their electrochemical performances are significantly different and the corresponding transport mechanisms at the electrolyte/electrode interface remain elusive. Here, we combine experimental and computational techniques to investigate the cathode interface in the presence of both functional polymer binders in comparison with the poly(vinylidene fluoride) (PVDF) binder as reference. A broad shoulder in the cyclic voltammogram accompanied by a poor rate performance of battery tests was observed for a LiFePO4 cathode with coordination-type ether-based polyimide (EPI) binder. In contrast, a LiFePO4 cathode with ion-type sulfonated polyimide (SPI) binder exhibits smaller concentration polarization, achieving satisfactory capacity at high current density. Simulations show that the ether-based binder strongly coordinates Li ions and thus slows the diffusion of Li ions. This leads to the reduction of the LIB electrochemical performance at a high C-rate. In contrast, the negative moiety of the SPI binder leads to less localization of Li ions, allowing a slightly higher Li-ion mobility. Conventional PVDF shows no affinity to Li ions, leading to less Li-ion accumulation at the electrode/electrolyte interface. Yet, the cathode surface covered with PVDF shows the lowest Li-ion diffusivity compared to those with the two types of Li-ion-conducting binders. Therefore, cathodes with SPI and PVDF binders show less polarization at the electrode interface and allow higher C-rate performance of LIBs. The combined results provide a comprehensive understanding of the mechanism of ion conduction in ion- and coordination-type Li-ion-conducting polymer binders. This gives valuable insight into the design of next-generation polymer materials for high-power LIBs.

20.
Chin J Nat Med ; 18(11): 844-849, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33308606

RESUMO

Four new polyhydroxylated steroids plaksterols A-D (1-4), together with two known related steroids ergost-7,9(11),22-trien-3ß,5α,6α-triol (5) and ergosta-6ß-methoxy-7,22-diene-3ß,5α-diol (6), were isolated from methanol extract of the South China Sea marine sponge Plakortis sp. Their structures were identified by spectroscopic analysis, including NMR, MS, and IR. The cytotoxicity of the polyhydroxylated steroids were evaluated, and compound 6 showed moderate inhibitory activities against K562, HL-60 and BEL-7402 cells.


Assuntos
Plakortis/química , Esteroides/química , Animais , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Oceano Pacífico , Esteroides/isolamento & purificação , Esteroides/farmacologia
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